Severe and fatal COVID‐19 is characterised by increased circulating glucagon like peptide 1 and procalcitonin modulated by type 2 diabetes

• Published in: Diabetes/metabolism research and reviews Vol. 39; no. 6; pp. e3635 - n/a
• Main Authors: Bloch, Olga, Kobi, Perl, Ben Shimol, Ariel, Rotmensh, Assaf, Kagansky, Dana, Zelnik‐Yovel, Dana, Yehudah, Gilad Ben, Cantrell, Dror, Rapoport, Micha J.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2023
• Subjects: COVID-19; COVID‐19 severity; Diabetes; Diabetes mellitus (non-insulin dependent); diabetic; endogenous GLP‐1 response; Endotoxemia; Glucagon; IL‐6; Immune response; Inflammation; Innate immunity; Interleukin 6; nondiabetic; Peptides; Plasma levels; Procalcitonin; Sepsis; Severe acute respiratory syndrome coronavirus 2; diabetic; procalcitonin; COVID-19 severity; endogenous GLP-1 response; IL-6; nondiabetic
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.3635

Aims Endotoxemia commonly occurs in severe and fatal COVID‐19, suggesting that concomitant bacterial stimuli may amplify the innate immune response induced by SARS‐CoV‐2. We previously demonstrated that the endogenous glucagon like peptide 1 (GLP‐1) system in conjunction with increased procalcitonin (PCT) is hyperactivated in patients with severe Gram‐negative sepsis and modulated by type 2 diabetes (T2D). We aimed to determine the association of COVID‐19 severity with endogenous GLP‐1 activation upregulated by increased specific pro‐inflammatory innate immune response in patients with and without T2D. Materials and Methods Plasma levels of total GLP‐1, IL‐6, and PCT were estimated on admission and during hospitalisation in 61 patients (17 with T2D) with non‐severe and severe COVID‐19. Results COVID‐19 patients demonstrated ten‐fold increase of IL‐6 levels regardless of disease severity. Increased admission GLP‐1 levels (p = 0.03) accompanied by two‐fold increased PCT were found in severe as compared with non‐severe patients. Moreover, GLP‐1 and PCT levels were significantly increased in non‐survived as compared with survived patients at admission (p = 0.01 and p = 0.001, respectively) and at 5 to 6 days of hospitalisation (p = 0.05). Both non‐diabetic and T2D patients demonstrated a positive correlation between GLP‐1 and PCT response (r = 0.33, p = 0.03, and r = 0.54, p = 0.03, respectively), but the intensity of this joint pro‐inflammatory/GLP‐1 response was modulated by T2D. In addition, hypoxaemia down‐regulated GLP‐1 response only in T2D patients with bilateral lung damage. Conclusions The persistent joint increase of endogenous GLP‐1 and PCT in severe and fatal COVID‐19 suggests a role of concomitant bacterial infection in disease exacerbation. Early elevation of endogenous GLP‐1 may serve as a new biomarker of COVID‐19 severity and fatal outcome.